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Enzyme
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Query: EC:1.8.1.4 (
diaphorase
)
2,754
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The enzyme isocitrate dehydrogenase (
IDH
, EC 1.1.1.42) can exhibit activation by one of its products, NADPH. This activation is competitively inhibited by the substrate NADP+, whereas NADPH competes with NADP+ for the catalytic site. Experimental observations briefly presented here have shown that if
IDH
is coupled to another enzyme,
diaphorase
(
EC 1.8.1.4
), which transforms NADPH into NADP+, the system can attain either one of two stable states, corresponding to a low and a high NADPH concentration. The evolution toward either one of these stable states depends on the time of addition of
diaphorase
to the medium containing
IDH
and its substrate NADP+. We present a theoretical and numerical analysis of a model for the
IDH
-
diaphorase
bienzymatic system, based on the regulatory properties of
IDH
. The results confirm the occurrence of bistability for parameter values derived from the experiments. Depending on the total concentration of NADP+ plus NADPH and the concentration of
IDH
, the system can either admit a single steady state or display bistability. We obtain an expression for the critical time t*, before which
diaphorase
addition leads to the lower steady state and after which addition of the enzyme leads to the upper steady state of NADPH. The analysis is extended to the case where the second substrate of
IDH
, isocitrate, is consumed in the course of the reaction without being regenerated. Bistability occurs only as a transient phenomenon in these conditions.
...
PMID:Bistability in the isocitrate dehydrogenase reaction: an experimentally based theoretical study. 951 21
We analyze the dynamics of a bienzymatic system consisting of isocitrate dehydrogenase (
IDH
, EC. 1.1.1.42), which transforms NADP+ into NADPH, and of
diaphorase
(DIA,
EC 1.8.1.4
), which catalyzes the reverse reaction. Experimental evidence as well as a theoretical model showed the possibility of a coexistence between two stable steady states in this reaction system G.M. Guidi et al. Biophys. J. 74 (1998) 1229-1240[, owing to the regulatory properties of
IDH
. Here we extend this analysis by considering the behavior of the model proposed for the
IDH
-DIA bienzymatic system in conditions where the system is open to an influx of its substrates isocitrate and NADP+ and to an efflux of all metabolic species. The analysis indicates that in addition to different modes of bistability (including mushrooms and isolas), sustained oscillations can be observed in such conditions. These results point to the isocitrate dehydrogenase reaction coupled to
diaphorase
as a suitable candidate for further experimental and theoretical studies of bistability and oscillations in biochemical systems. The results obtained in this particular bienzymatic system bear on other enzymatic systems possessing a cyclical nature, which are known to play significant roles in a variety of metabolic and cellular regulatory processes.
...
PMID:Oscillations and bistability predicted by a model for a cyclical bienzymatic system involving the regulated isocitrate dehydrogenase reaction. 1067 20
Considered is a bienzymatic system consisting of isocitrate dehydrogenase (
IDH
, EC 1.1.1.42), which transforms NADP(+) into NADPH, and of
diaphorase
(DIA,
EC 1.8.1.4
), which catalyzes the reverse reaction. Experimental evidence as well as a theoretical model show the possibility of a coexistence between two stable steady states in this reaction system. The phenomenon originates from the regulatory properties of
IDH
. We extend the analysis of a theoretical model proposed for the
IDH
-DIA bienzymatic system and investigate the occurrence of different modes of bistability, with or without hysteresis, i.e. in the presence of two or only one limit point bounding the domain of multiple steady states. The analysis indicates that the two types of bistability may sometimes be observed sequentially as a given control parameter is progressively increased. We further obtain conditions in which sustained oscillations develop in the model. These results establish the isocitrate dehydrogenase reaction coupled to
diaphorase
as a suitable candidate for further experimental and theoretical studies of bistability and oscillations in biochemical systems.
...
PMID:From bistability to oscillations in a model for the isocitrate dehydrogenase reaction. 1702 7
